The well-recognized immunosuppressive effects of both alcohol and HIV infection highlight the importance of understanding the interactions between these two immunocompromising factors. Alcohol abuse increases host susceptibility to infections by impairing innate and specific limbs of the immune system. We found alcohol to suppress the tumor necrosis factor-( (TNF() response to ntrapulmonary and systemic lipopolysaccharide (LPS) challenge. Subsequent experiments revealed that, when alcohol is added directly to peripheral blood mononuclear cells, it also suppresses the LPS-induced TNF( response. Alcohol substantially suppressed the LPS-induced TNF( response to alveolar macrophage and blood under in vitro conditions. Ethanol suppression of this response was similar in cells from both control and SIV-infected animals. These results suggest that alcohol might cause a further impairment of host defense in SIV-infected animals and result in an earlier and/or increased incidence of opportunistic infections in these animals. Work in HIV-infected patients indicate that such infections can increase viral replication, thereby accelerating disease progression. We examined the effect of in vitro alcohol on the functional state of blood neutrophils because other studies show that alcohol impairs neutrophil function and that both alcohol and HIV disease can result in neutropenia. When alcohol was added to blood containing neutrophils, it impaited f-met-leu-phe stimulated cell surface expression of the (2-integrin CD11b by neutrophils from uninfected and SIV-infected animals to a similar degree. Neutrophil phagocytosis, in the absence and presence of alcohol, was also examined in blood from uninfected and SIV-infected animals. Neutrophils from SIV-infected animals exhibited a 62% greater capacity to phagocytize latex beads when compared with neutrophils obtained from control animals. However, the addition of alcohol suppressed this activity, regardless of the neutrophil source. These studies show that, as in human beings, alcohol compromises several aspects of the innate immune system that could be improtant in protecting the animal from opp ortunistic infections. The close similarities between HIV disease in people and SIV infection in rhesus monkeys, together with out initial findings, demonstrate the appropriateness of the rhesus monkey SIV model for the study of the potential impact of alcohol on HIV/AIDS. FUNDING Base Grant PUBLICATIONS None